A cholesterol-binding domain in STIM1 modulates STIM1-Orai1 physical and functional interactions
Por:
Pacheco, Jonathan, Dominguez, Laura, Bohorquez-Hernandez, A., Asanov, Alexander, Vaca, Luis
Publicada:
27 jul 2016
Categoría:
Multidisciplinary
Resumen:
STIM1 and Orai1 are the main components of a widely conserved Calcium
influx pathway known as store-operated calcium entry (SOCE). STIM1 is a
calcium sensor, which oligomerizes and activates Orai channels when
calcium levels drop inside the endoplasmic reticulum (ER). The series of
molecular rearrangements that STIM1 undergoes until final activation of
Orai1 require the direct exposure of the STIM1 domain known as SOAR
(Stim Orai Activating Region). In addition to these complex molecular
rearrangements, other constituents like lipids at the plasma membrane,
play critical roles orchestrating SOCE. PI(4,5)P-2 and enriched
cholesterol microdomains have been shown as important signaling
platforms that recruit the SOCE machinery in steps previous to Orai1
activation. However, little is known about the molecular role of
cholesterol once SOCE is activated. In this study we provide clear
evidence that STIM1 has a cholesterol-binding domain located inside the
SOAR region and modulates Orai1 channels. We demonstrate a functional
association of STIM1 and SOAR to cholesterol, indicating a close
proximity of SOAR to the inner layer of the plasma membrane. In
contrast, the depletion of cholesterol induces the SOAR detachment from
the plasma membrane and enhances its association to Orai1. These results
are recapitulated with full length STIM1.
Filiaciones:
Pacheco, Jonathan:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico
Dominguez, Laura:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Quim Fis, Ciudad Univ, Mexico City 04510, DF, Mexico
Bohorquez-Hernandez, A.:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico
Asanov, Alexander:
TIRFLabs Inc, 106 Grendon Pl, Cary, NC 27519 USA
Vaca, Luis:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico
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